This proposal is to study the cellular mechanisms involved in the chemical modulation of a well-characterized invertebrate central pattern generator, the gastric mill network of the lobster Panulirus interruptus. Three neuromodulators, known to be present in the lobster, will be studied. The pentapeptide proctolin, a CCK-like peptide and the conventional neurotransmitter acetylcholine (ACH) which has a modulatory action on the stomatogastric ganglion, will be used. These substances produce profound changes in the motor pattern by altering the cellular and synaptic properties of individual cells in the gastric mill network. The aim of this proposal is to determine which cells respond to these modulators and what mechanisms are involved. We will first characterize the ionic mechanisms involved in the modulation of specific gastric mill neurons in situ. We will compare the results with similar experiments performed in vitro. We will continue our purification of a family of CCK-like peptides found in lobsters until we have enough pure substance to sequence and use for physiological studies. Finally we will characterize a family of three ACH receptor molecules, two nicotinic and one muscarinic, which are involved in diverse functions. We are particularly interested in determining if any of the receptors are themselves modulatable and if so how their molecular structure differs from other known ACH receptor molecules.